Use of coagulation proteins to lyse clots

Abstract

The present invention relates to the use of coagulation proteins for the lysis of blood clots. More specifically, the present invention provides a method for accelerating the dissolution of a blood clot through the administration of at least one coagulation protein comprising a basic C-terminal amino acid, wherein the coagulation protein may be a derivative of Factor X, Factor V or a combination thereof. Pharmaceutical compositions for the treatment and prophylaxis of blood clots are also provided, wherein, the methods and products of the present invention advantageously accelerate clot dissolution while potentially minimizing the adverse side-effects, such as hemorrhaging, seen with other clot dissolving agents. The present invention also provides a method for detecting a fibrinolytic potential in a subject.

1 . A method for accelerating blood clot dissolution in a subject in need thereof, the method comprising administering to said subject at least one coagulation protein comprising a basic C-terminal amino acid in an amount effective to dissolve said blood clot. 
   
   
       2 . The method of  claim 1 , wherein said protein is an anionic phospholipid-binding protein. 
   
   
       3 . The method of  claim 1 , wherein said subject has a condition selected from the group consisting of thrombosis, platelet hyperactivity, cardiac ischemia, wound, cardiovascular disease, atherosclerosis, myocardial infarction and a combination thereof. 
   
   
       4 . The method of  claim 3 , wherein said subject is susceptible to said condition and said administering is prophylactic. 
   
   
       5 . The method of  claim 1 , wherein said at least one coagulation protein is a derivative of Factor X. 
   
   
       6 . The method of  claim 5 , wherein said derivative is selected from Factor Xaα, Xaβ, Xaγ, or a combination thereof. 
   
   
       7 . The method of  claim 1 , wherein said at least one coagulation protein is a derivative of Factor V. 
   
   
       8 . The method of  claim 7 , wherein said derivative is Factor Va. 
   
   
       9 . The method of  claim 1 , wherein said at least one coagulation protein comprises a derivative of Factor X and a derivative of factor V. 
   
   
       10 . The method of  claim 5 , wherein said derivative of Factor X is formulated in a pharmaceutical composition. 
   
   
       11 . The method of  claim 7 , wherein wherein said derivative of Factor V is formulated in a pharmaceutical composition. 
   
   
       12 . The method of  claim 10 , wherein said pharmaceutical composition further comprises a fibrinolytic agent selected from the group consisting of tissue plasminogen activator, urokinase, streptokinase and a combination thereof. 
   
   
       13 . The method of  claim 10 , wherein said pharmaceutical composition further comprises an inhibitor of thrombin selected from the group consisting of hirudin, bivalirudin, lepirudin and heparin and a combination thereof. 
   
   
       14 . The method of  claim 11 , wherein said pharmaceutical composition further comprises a fibrinolytic agent selected from the group consisting of tissue plasminogen activator, urokinase, streptokinase and a combination thereof. 
   
   
       15 . The method of  claim 11 , wherein said pharmaceutical composition further comprises an inhibitor of thrombin selected from the group consisting of hirudin, bivalirudin, lepirudin and heparin and a combination thereof. 
   
   
       16 . A method for detecting a fibrinolytic potential in a subject, the method comprising:
 a) obtaining a blood sample from said subject; and   b) measuring a relative concentration of a coagulation protein selected from a coagulation protein comprising a basic C-terminal amino acid, a derivative of a coagulation protein comprising a basic C-terminal amino acid or a combination thereof.   
   
   
       17 . A pharmaceutical composition comprising a coagulation protein for the treatment or prophylaxis of blood clotting, wherein said coagulation protein comprises a basic C-terminal amino acid.